Gln48His Is the Prevalent Myocilin Mutation in Primary Open Angle and Primary Congenital Glaucoma Phenotypes in India

Abstract

Abstract: : Purpose: Mutations in the Myocilin gene (MYOC) have been implicated in cases of juvenile and adult–onset primary open angle glaucoma (POAG) worldwide. Based on multiple reports for the occurrence of one such mutation, Gln48His (c.144 G>T; HGMD accession no. CM023962) among Indian POAG patients, we wanted to estimate its prevalence in cases of POAG and primary congenital glaucoma (PCG) in India and assess its role in the causation of the disease. Methods: Four hundred cases (200 of POAG and 200 of PCG) presenting from different ethnic backgrounds and geographical regions of India along with 300 ethnically matched normal controls were recruited. The Gln48His mutation was screened by RFLP analysis by digesting the PCR amplicons with TaaI enzyme followed by confirmation of the c.144 G>T change by direct sequencing. Results: The Gln48His mutation was detected in 9 different glaucoma patients (four POAG and five PCG). While all four POAG cases were heterozygous, among PCG cases, four were heterozygous and one exhibited homozygous genotype for the mutation. One each of POAG and PCG patients also exhibited a heterozygous CYP1B1 mutation (c.1656C>T, Pro437Leu) and (c.1449G>A, Arg368His), respectively, indicating a digenic inheritance. None of the normal controls contained either the MYOC or CYP1B1 mutation(s). Conclusions: The myocilin mutation, Gln48His, represents an allelic condition involving a spectrum of glaucoma phenotypes in Indian populations, and could be a potential risk factor towards disease predisposition among patients of Indian origin. The study also highlights the role of MYOC as a candidate in different glaucoma subtypes that needs to be investigated further.

Keywords: candidate gene analysis • gene screening • mutations